Inhibited cell death, NF-kappaB activity and increased IL-10 in TCR-triggered thymocytes of transgenic mice overexpressing the glucocorticoid-induced protein GILZ.
Glucocorticoids promote thymocyte apoptosis and modulate transcription of several genes including GILZ, which is strongly up-regulated in the thymus. We used transgenic mice overexpressing GILZ in the T-cell lineage to investigate TCR-triggered functions of GILZ-overexpressing thymocytes. TCR-triggered apoptosis, but not glucocorticoid-induced apoptosis, was inhibited in transgenic mice compared to their controls. In vivo anti-CD3 administration did not reduce CD4(+)CD8(+) thymocyte number. Analysis of TCR-triggered molecular changes indicated that p65 NF-kappaB nuclear translocation and DNA binding activity was inhibited in transgenic mice, which might be linked with apoptosis inhibition. IL-10 release increased whereas release of IL-2, IFN-gamma, IL-13 and IL-4 remained unchanged. These results support the hypothesis that GILZ regulates, at least in part, T-cell development by influencing thymus function at cellular and molecular levels.